Polymorphisms in the tumor necrosis factor alpha and interleukin 1-beta promoters with possible gene regulatory functions increase the risk of preterm birth.
OBJECTIVE
To investigate the relation between 19 selected single nucleotide polymorphisms in three cytokine genes, tumor necrosis factor alpha (TNFA), interleukin 1-beta (IL1B) and interleukin 6 (IL6) and preterm birth (<37 weeks' gestation).


METHODS
Case-control association study.


METHODS
A total of 117 singleton pregnant Danish Caucasian women, including 62 preterm birth cases and 55 controls (birth>or=37 weeks).


METHODS
Genotyping was performed using TaqMan probes and traditional sequencing. Descriptive statistics were carried out with Fisher's exact test and Wilcoxon rank-sum test. All genetic data were tested for Hardy-Weinberg equilibrium and analyzed using logistic regression, 2x2 proportions or chi(2). Haplotypes were estimated for each gene and permutation used for association testing.


RESULTS
Women carrying the TNFA -857 C>T rare allele (T) and those homozygous for the IL1B -31 T>C and IL1B -511 C>T rare alleles (C and T) have an increased risk of preterm birth with OR 3.1 (95% CI: 1.0-10.3) and OR 6.4 (95% CI: 1.3-60.5), respectively. Two estimated TNFA haplotypes were associated with preterm birth with OR 3.1 (p=0.037) and OR 2.7 (p=0.045).


CONCLUSIONS
Polymorphisms in the cytokine genes TNFA and IL1B may increase the risk of preterm birth, possibly by a dysregulation of the immune system in pregnancy.
Hollegaard
Mads Vilhelm
MV
Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark. mvh@ssi.dk
Grove
Jakob
J
Thorsen
Poul
P
Wang
Xiaobin
X
Mandrup
Susanne
S
Christiansen
Michael
M
Norgaard-Pedersen
Bent
B
Wojdemann
Karen R
KR
Tabor
Ann
A
Attermann
Jorn
J
Hougaard
David Michael
DM
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics; D016015:Logistic Models; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha